Hindawi Gastroenterology Research and Practice Volume 2019, Article ID 6532876, 7 pages https://doi.org/10.1155/2019/6532876 Research Article The Protective Effect of Teprenone on Aspirin-Related Gastric Mucosal Injuries Jing Zhao ,1,2 Yihong Fan ,1,2 Wu Ye ,1 Wen Feng ,1 Yue Hu ,1,2 Lijun Cai ,1,2 and Bin Lu 1,2 1Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China 2Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China Correspondence should be addressed to Bin Lu; [email protected] Received 16 July 2018; Accepted 28 November 2018; Published 18 June 2019 Academic Editor: Haruhiko Sugimura Copyright © 2019 Jing Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Aspirin usage is associated with increased risk of gastrointestinal bleeding. The present study explored the potential of teprenone, an antiulcerative, in preventing aspirin-related gastric mucosal injuries. Methods. 280 patients with coronary diseases, naïve to aspirin medication, were admitted between 2011 and 2013 at the First Affiliated Hospital of Zhejiang Chinese Medical University and randomized into two groups (n = 140). The aspirin group received aspirin enteric-coated tablets 100 mg/day, while the aspirin+teprenone group received teprenone 50 mg 3 times/day along with aspirin. The patients were recorded for gastrointestinal symptoms and gastric mucosal injuries during a follow-up period of 12 months with 3-month intervals. Results. During the 3-month follow-up, no significant difference was observed in the incidence rate of gastrointestinal symptoms between the two groups (P =0498). However, the incidence rate of gastrointestinal symptoms was significantly lower in the aspirin+teprenone group than in the aspirin group during the follow-ups at 6 months (P =0036) and 12 months (P =0036). The incidence rate of gastric mucosal injuries in the aspirin group was significantly increased at 12 months compared to that at 3 months (P =0016). The incidence rates at 12 months and cumulative for the entire follow-up period in the aspirin+teprenone group were both significantly lower than those of the aspirin group (P =0049 and P =0001, respectively). Conclusion. Long- term use of low-dose aspirin causes varying degrees of gastric mucosal damages and gastrointestinal symptoms; the severity will increase within a certain range with the extension of medication duration. Teprenone mitigates the gastrointestinal symptoms caused by low-dose aspirin, lowering both the incidence and severity of gastric mucosal injuries and exerting a positive protective effect. 1. Introduction The major benefits in male patients included lowered risks of myocardial infarct, while reduced risks of ischemic strokes Aspirin (acetylsalicylic acid) can inhibit platelet aggregation were presented in female patients [4, 5]. In addition to the by suppressing the production of platelet thromboxane A2. demonstrated benefits of low-dose aspirin in the treatment Therefore, it serves as an antipyretic analgesic, anti-inflam- of cardiovascular diseases, the usage of aspirin has been matory, and antirheumatic agent [1]. For decades, aspirin strongly debated owing to an increased risk of gastrointesti- at a low dose has been used as a secondary agent in the treat- nal bleeding [6]. Gastrointestinal symptoms are the most ment and prevention of cardiovascular anomalies [2, 3]. In commonly observed adverse effects of aspirin, and long- addition, the use of aspirin for the primary prevention of car- term usage can lead to gastric mucosal injuries including diovascular disease had demonstrated a significant reduction ulcers and bleeding. However, the removal of aspirin therapy in major cardiovascular events in the drug-using population. has been associated with a higher mortality rate [7]. 2 Gastroenterology Research and Practice Therefore, one of the challenges in clinical practice and fram- of other nonsteroidal anti-inflammatory drugs (NSAIDs), ing health policy is to identify the measures for preventing antacids, or bismuth medications 2 weeks before the study gastric mucosal injuries caused by long-term use of aspirin or during the study period; (c) patients with histories of and the procedures to determine if the benefits outweigh upper gastrointestinal surgeries or upper gastrointestinal the associated risks [8]. hemorrhage, or suspicions or evidence of malignancies The application of misoprostol, omeprazole, lansopra- (alarm symptoms or signs); (d) patients with severe compli- zole, famotidine, and proton pump inhibitors has been inves- cations of heart, lung, liver, kidney, blood, endocrine, or tigated for their efficacy in preventing aspirin-induced other diseases that may cause damages to the gastrointestinal gastrointestinal injuries [9–13]. However, the choice of these tracts; (e) pregnant or lactating women; (f) patients with his- drugs for preventing the gastrointestinal injuries of patients tories of allergy to the study drugs; (g) patients who partici- using aspirin remains controversial. According to the recent pated in other clinical studies within 1 month prior to the guidelines [14], PPIs are recommended for patients with high study; (h) patients who stopped using or changed the dose gastrointestinal (GI) risk who could not avoid using nonste- of aspirin during the study period; and (i) patients who were roidal anti-inflammatory drugs (NSAIDs). For patients at unable to maintain regular follow-ups as per the protocol or low GI risk, PPIs are not recommended, considering its comply with all the study protocols. potential adverse effects, high expense, and overuse in clinical This study was approved by the Ethics Committee of the settings [15]. Currently, there is paucity in therapeutics First Affiliated Hospital of Zhejiang Chinese Medical Univer- investigated for the prevention of aspirin-induced gastroin- sity (approval number: 2012043), and signed informed con- testinal complications for these low-GI-risk patients who sent forms were obtained from all the enrolled patients. are not recommended to use PPIs [16]. Thus, there is an urgent need for several randomized control trials and obser- 2.2. Grouping. Patients were randomized into two groups ffi vational studies to investigate the e cacy of additional drugs using the random number table. For the 140 patients in the that could be used by these patients in the prevention of aspirin group, a daily medication of aspirin enteric-coated aspirin-associated complications. tablets (Bayer Pharmaceuticals, Germany), 100 mg, was pre- One of the possible therapeutics to reduce aspirin- scribed, whereas for the other 140 patients in the aspirin induced bleeding could be the usage of an antiulcerative. +teprenone group, oral medication of teprenone (Eisai Co., Teprenone (6,10,14,18-tetramethyl-5,9,13,17-nonadeca-tet- Ltd., Japan), 50 mg 3 times/day at 2 h after meals was admin- ff raene-2-one), an antiulcerative, exerts a protective e ect on istered in addition to that of aspirin. The study flowchart is gastric mucosal injuries by promoting gastric mucus secre- shown in Figure 1. tion, cell regeneration, and increased gastric blood flow [17–19] and is reported to be the most common gastromuco- protective agent in clinical usage with a low incidence of side 2.3. Data Collection. Details regarding the gastrointestinal effects [20]. Moreover, our previous study has also shown symptoms, gastric mucosal injuries, diet habits, alcohol and that teprenone can reduce NSAID-related acute gastric and tobacco habits, presence or absence of family history of gas- small intestinal mucosal injuries in rats [21, 22]. Therefore, tric cancers, and disease history of the enrolled patients were this study investigated the potential of teprenone in the pro- asked and recorded. Gastrointestinal symptoms included upper abdominal tection against aspirin-induced gastric mucosal injuries in fl patients with a long-term routine-dose usage of aspirin. pain and discomfort, abdominal distension, acid re ux, belching, nausea, changes in stool color, and results of the fecal occult blood test. 2. Materials and Methods Gastric mucosal injuries were assessed based on the clin- fi 2.1. Study Subjects. A total of 280 patients with coronary dis- ical manifestations or the gastroscopic ndings (the Lanza eases who were naïve to routine-dose aspirin and admitted at Endoscopic Scoring System was used to assess endoscopic ffi damage only for those willing to undergo gastroscopy [23]), the outpatient department of the First A liated Hospital of ’ Zhejiang Chinese Medical University between 2011 and and data regarding patients gastric mucosal erosions or ulcers were recorded. 2013 were enrolled based on the following inclusion and ’ exclusion criteria. Patients incidences of gastrointestinal symptoms were The inclusion criteria included (a) patients who require recorded every week during the therapeutic period, and the long-term usage of low-dose (<200 mg/day) aspirin enteric- fecal occult blood test was performed at the monthly fol- coated tablets for the prevention or treatment of cardiovascu- low-up. lar and cerebrovascular diseases, excluding other combina- The three follow-up visiting time points were 3, 6, and 12 tions; (b) patients without abnormal results of routine